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G.I. Liou, A.B. El–Remessy, M. Al–Shabrawey, Y. Khalifa, R.B. Caldwell; Neuroprotective and Blood–Retinal Barrier–Preserving Effects of Cannabidiol in Experimental Diabetes . Invest. Ophthalmol. Vis. Sci. 2005;46(13):450.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Diabetic retinopathy is characterized by blood–retinal barrier (BRB) breakdown and neurotoxicity. BRB breakdown has been associated with increases in oxidative stress and expression of pro–inflammatory cytokines. Neurotoxicity involves glutamate–induced oxidative stress and neuronal cell death. P38 MAP kinase, a down stream target of TNF–alpha and oxidative stress has been shown to be a key regulator of vascular permeability and retinal neural cell death. Cannabinoids, generally believed to have properties of anti–inflammation and anti–oxidation, have not been tested in diabetes due to their psychotropic activity. In the present study, the anti–oxidant and anti–inflammatory effects of a non–psychotropic cannabinoid, Cannabidiol (CBD) are examined in experimental diabetes. Methods: Rats were rendered diabetic by streptozotocin injection and were treated by CBD or vehicle for 1, 2, 4, or 7 weeks. Diabetes–induced retinal cell death was determined by TUNEL. BRB function was measured by quantifying extravasation of BSA–fluorescein. Oxidative stress was determined by an assay for lipid peroxidation and measurement of reactive oxygen species. Expression of retinal ICAM–1, TNF–alpha and p38 MAP kinase were determined by immunohistochemistry, ELISA or Western blot analyses. Results: Diabetes induced significant increases in oxidative stress, retinal neural cell death and vascular permeability. That effect was associated with activation of p38 MAP kinase and increased levels of TNF–alpha and ICAM–1 expression. CBD treatment significantly reduced oxidative stress and prevented retinal cell death and vascular permeability increase in the diabetic retina. Moreover, diabetes–induced activation of p38 MAP kinase was significantly reduced by CBD. The anti–inflammatory activity of CBD was demonstrated by its effect in reducing the levels of TNF–α and ICAM–1. Conclusions: These results demonstrate that CBD treatment reduces neurotoxicity and BRB breakdown in diabetic animals through both its activities in anti–oxidation and anti–inflammation by a process that may involve inhibition of p38 MAP kinase.
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